• Dextroamphetamine sulfate administered intravenously in the morning to 11 unmedicated depressed patients suppressed previously elevated plasma cortisol levels to normal in 90 minutes, a fall of 33% from baseline. Ten other depressed patients, without amphetamine, maintained high cortisol levels during the same time period. In each of five normal young men, amphetamine identically administered stimulated a rise in cortisol between 15 and 30 minutes after infusion, an acute response absent in ten of the 11 depressed patients; by 90 minutes after amphetamine administration, plasma cortisol had fallen to normal and identical levels in both groups. Since noradrenalin normally inhibits hypothalamic corticotropin releasing factor (and adrenocorticotropic hormone) secretion, a noradrenergic deficit may account for cortisol hypersecretion in depression; amphetamine may transiently "correct" this deficit in depressed patients, thereby reducing their cortisol secretion.